Related Experiment Video
Updated: Apr 30, 2026
06:21
Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer
Published on: May 10, 2024
1.6K
NFE2L2 polymorphisms, mortality, and metabolism in the general population
Sylwia M Figarska1, Judith M Vonk1, H Marike Boezen2
1Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Physiological Genomics
|May 3, 2014
Summary
The nuclear factor (erythroid-derived 2)-like 2 (NRF2) gene is linked to reduced mortality from all causes, cardiovascular disease, and COPD. Specific NRF2 gene variations also correlate with lower triglyceride levels, highlighting its role in health.
Area of Science:
- Genetics and Molecular Biology
- Cardiovascular Disease Epidemiology
- Respiratory Disease Research
Background:
- The nuclear factor (erythroid-derived 2)-like 2 (NFE2L2 or NRF2) gene regulates key cellular processes including detoxification and lipid homeostasis.
- Previous research suggests NRF2 involvement in the pathophysiology of atherosclerosis and chronic obstructive pulmonary disease (COPD).
- Understanding the genetic associations of NRF2 with mortality and lipid profiles is crucial for public health.
Purpose of the Study:
- To investigate the relationship between NFE2L2 gene variations and all-cause, cardiovascular, and COPD mortality.
- To examine the association of NFE2L2 single nucleotide polymorphisms (SNPs) with triglyceride and cholesterol levels.
- To explore potential protective effects of specific NRF2 genotypes against major health outcomes.
Main Methods:
- Genotyping of five tagging SNPs in the NFE2L2 gene (rs4243387, rs2364723, rs13001694, rs1806649, rs6726395) in 1,390 individuals from the Vlagtwedde-Vlaardingen cohort.
- Longitudinal follow-up for vital status evaluation over 18 years (1989/1990 to 2008).
- Statistical analysis using Cox proportional hazards regression for mortality and linear regression for lipid levels.
Main Results:
- Carriers of the minor allele for SNP rs13001694 showed a significantly reduced risk of all-cause mortality (HR 0.8).
- Minor allele carriers of SNP rs2364723 exhibited a significantly reduced risk of cardiovascular mortality (HR 0.5), with consistent findings across subgroups.
- Carriers of the minor allele for SNP rs1806649 demonstrated a markedly reduced risk of COPD mortality (HR 0.3), and rs2364723 was associated with lower triglyceride levels.
Conclusions:
- This study provides the first evidence in humans linking specific NFE2L2 gene variations to a reduced risk of all-cause, cardiovascular, and COPD mortality.
- The findings suggest a significant role for NRF2 genetic variants in modulating mortality risks and lipid metabolism.
- Further research into NRF2 pathways could offer novel therapeutic targets for cardiovascular and respiratory diseases.
More Related Videos
Related Concept Videos
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
159
Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
159
01:27Pharmacogenetics of Drug Metabolism: Overview
194
Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...
194
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
81
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
81
01:27Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
94
Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
94
01:18Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Metabolism
400
Geriatric patients show significant variation in how their bodies process medications, which can change how effective and safe treatments are. The liver is the primary organ where drug metabolism occurs, involving two main types of chemical reactions: phase I and II. Phase I metabolism is driven by the cytochrome P450 enzyme system, which includes key types such as CYP3A, CYP2D6, and CYP2C9. Research indicates that while aging doesn't notably alter the levels or activity of these enzymes, it...
400
01:16Drug toxicity: Idiosyncratic Reactions
220
Idiosyncratic drug reactions represent abnormal chemical responses that vary significantly among individuals, ranging from extreme sensitivity to low doses to insensitivity to high doses. These reactions often occur due to the drug's covalent binding with serum proteins, forming a foreign hapten that triggers an immunotoxicological response. The variability in drug reactions has a strong pharmacogenetic foundation, with genetic differences crucial in how individuals metabolize drugs. For...
220